Author: [email protected]

Celsion Corporation Announces Progress with ThermoDox® Development Efforts in China and Asia Pacific

On December 16, 2016 Celsion Corporation (NASDAQ:CLSN) reported an update on its Phase III OPTIMA program for ThermoDox, Celsion’s proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC) (Press release, Celsion, DEC 16, 2016, View Source [SID1234517095]). The Phase III OPTIMA Study is expected to enroll up to 550 patients at up to 75 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus standardized RFA alone.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company recently met with the China Food and Drug Administration (CFDA) to discuss the ongoing Phase 3 OPTIMA program and regulatory pathway for ThermoDox in China. During the meeting, Celsion presented the final overall survival data from the Chinese patient cohort of the HEAT study, which demonstrated a survival benefit in patients treated with ThermoDox plus optimized RFA versus optimized RFA alone. The CFDA informed Celsion that if the ongoing Phase 3 OPTIMA trial is successful, the trial could serve as the basis for a direct regulatory filing in China without the need to file for prior approval in the U.S. or European Union which is currently required for foreign company application. This would allow the Company to accelerate its plans for a regulatory filing in China and, if approved, provide for a significantly earlier launch date in China than originally expected.

"We are building momentum with our efforts for ThermoDox in the Asia Pacific region, particularly China, which represents a significant market opportunity with over 50% of new diagnosed cases of this devastating cancer," stated Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "All Chinese sites will be fully activated by early 2017, enrollment is on pace to meet our objective of fully enrolling the trial by the first quarter of 2018, and we have advanced our manufacturing in China with Hisun to support a potential future launch in this region with impressive gross margins. We believe that the remarkable data from the Chinese cohort of the HEAT study underscores the potentially curative nature of ThermoDox in patients with primary liver cancer, and we are pleased that the CFDA has both recognized its potential and offered a straightforward path to a regulatory filing in China."

In support of its efforts in China, Celsion reported that recent bioequivalence studies of ThermoDox produced in China by Hisun are equivalent to batches of ThermoDox produced at its United States manufacturing site.

In addition, Celsion reported that the Company’s management team recently met with the Ministry of Health in Vietnam and based on that meeting, it will move forward with launching additional trial sites for the OPTIMA study in the country. Celsion expects to have approximately 5 additional clinical trial sites in Vietnam activated by early 2017. Vietnam represents a significant market for ThermoDox where HCC incidence rates are among the world’s highest.

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 75 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus standardized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).

Aptevo Therapeutics Announces Publication of Phase 2 Clinical Data for Otlertuzumab

On December 16, 2016 Aptevo Therapeutics Inc. (Nasdaq:APVO) a biotechnology company focused on developing novel oncology and hematology therapeutics, reported the publication of positive data from a Phase 2 clinical trial evaluating its proprietary humanized monospecific anti-CD37 protein therapeutic, otlertuzumab (Press release, Aptevo Therapeutics, DEC 16, 2016, View Source;p=irol-newsArticle&ID=2230353 [SID1234517094]). The results were recently published in the British Journal of Haematology (BJH).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We’re very encouraged by the Phase 2 data, which demonstrated a significant increase in median progression free survival, from approximately 10 to 16 months in patients receiving combination otlertuzumab/bendamustine therapy," said Marvin L. White, President and Chief Executive Officer. "These data, coupled with additional results from ongoing studies of otlertuzumab used in combination with current CLL therapies should help position otlertuzumab for a potential partnership to advance into Phase 3 clinical development."

The publication, entitled, "Randomized Phase 2 Study of Otlertuzumab and Bendamustine Versus Bendamustine in Patients with Relapsed Chronic Lymphocytic Leukemia," discusses the results of a multi-center Phase 2 clinical trial comparing the efficacy and safety of otlertuzumab in combination with bendamustine to bendamustine alone in patients with relapsed chronic lymphocytic leukemia (CLL). The data show an improved overall response rate and progression free survival with combination otlertuzumab/bendamustine therapy.

"While substantial advances in the treatment of CLL have been made over the last several years, there is still a significant unmet medical need for safe and effective new combination therapies to treat the many CLL patients that eventually will experience a relapse or discontinue therapy due to adverse events," remarked Dr. Scott Stromatt, Chief Medical Officer for Aptevo. "These latest data show the combination of otlertuzumab and bendamustine is well tolerated and significantly increases the response rate and PFS in patients with relapsed or refractory CLL. Consequently we are now exploring the utility of otlertuzumab in combination with additional CLL therapies to evaluate clinical benefit in distinct CLL patient subgroups."

The data published in BJH suggest that combination therapy with otlertuzumab may improve outcomes for CLL patients. In previous studies Aptevo has shown that otlertuzumab in combination with rituximab, obintuzumab or idelalisib is clinically active and appears to have a good safety and tolerability profile. Based on this promising body of data, Aptevo is further exploring its utility in subgroups of CLL patients who have either (i) not achieved a complete response after one year of therapy with ibrutinib, or (ii) in patients who are developing a resistant clone to ibrutinib but have not yet experienced a clinical relapse.

About the Phase 2 Clinical Trial
A total of 65 patients participated in the study with 32 receiving a combination of otlertuzumab and bendamustine and 33 receiving bendamustine alone. The primary endpoint in the clinical trial was overall response rate (ORR), as measured by the 2008 International Workshop on CLL. Secondary endpoints included an assessment of progression free survival (PFS) and safety.

Phase 2 Clinical Trial Results
The study demonstrated that otlertuzumab combined with bendamustine significantly increased overall response rate, which was 69% for the combination compared to 39% for bendamustine alone (p=0.025). In addition, the combination showed an improvement in median progression free survival, which was 15.9 months in the otlertuzumab/bendamustine combination treatment arm compared to 10.2 months in the bendamustine treatment arm (p=0.0192). Otlertuzumab in combination with bendamustine was generally well tolerated, although there was a higher incidence of pyrexia (34% vs. 12%) and neutropenia (59% vs. 39%) with the combination, however, this did not result in a higher incidence of severe (grade 3 or 4) infections.

The full publication in the British Journal of Haematology can be accessed online at View Source

Pre-clinical profile of reversible BTK inhibitor RXC005 presented at ASH 2016

On December 16, 2016 Redx Pharma Plc is pleased to announce that it has presented the pre-clinical profile of its reversible Bruton’s tyrosine kinase (BTK) inhibitor RXC005 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California, United States, on 5 December 2016 (Press release, Redx Pharma, DEC 16, 2016, View Source [SID1234524745]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Redx’s development candidate RXC005 is a novel, potent and selective, reversible BTK inhibitor with efficacy and equivalent potency against wild-type and cysteine-481 (C481) mutated BTK. First generation BTK inhibitors, such as Ibrutinib and Acalabrutinib, specifically target C481 within BTK and mutations at this site interfere with covalent drug binding. Several mutations have been reported and linked to cases of resistance that have emerged in patients with chronic lymphocytic leukaemia (CLL) progression following treatment with Ibrutinib. Redx’s reversible BTK inhibitor RXC005 aims to overcome this resistance mechanism by targeting both wild type and C481-mutated BTK.

The Company is progressing studies to prepare the RXC005 program for first-in-human clinical trials. The aim is to commence these trials late 2017.

Dr Neil Murray, CEO of Redx, said: We’re delighted to have presented the compelling pre-clinical profile of our reversible BTK inhibitor RXC005 at the ASH (Free ASH Whitepaper) 2016 meeting in San Diego.

RXC005 has the potential to become a potent therapy for chronic lymphocytic leukaemia patients by tackling the growing resistance to Ibrutinib treatment. We aim to initiate first-in-human clinical studies for RXC005 late 2017.

Further Details:
American Society of Hematology web site: View Source
Poster title: RXC005 (REDX08608), a Novel, Potent and Selective, Reversible BTK Inhibitor with Efficacy and Equivalent Potency Against Wild-Type and Mutant C481S BTK
Download the presentation poster: RXC005 (REDX08608) BTK Inhibitor

CHMP recommends EU conditional approval of Roche’s Alecensa (alectinib) for people with previously treated ALK-positive NSCLC

On December 16, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Medicines Agency (EMA) for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the use of Alecensa (alectinib) for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose disease has progressed following treatment with crizotinib(Press release, Hoffmann-La Roche, DEC 16, 2016, View Source [SID1234517093]). ALK-positive NSCLC occurs in approximately five percent of people with advanced NSCLC, translating to about 75,000 people globally being diagnosed with the disease per year. ALK-positive disease is more common in light or non-smokers.3,1 Based on this positive CHMP recommendation, a final decision regarding the conditional marketing authorisation is expected from the European Commission in the coming months.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Most people living with ALK-positive NSCLC develop resistance to the current standard of care, and nearly half see their tumours spread to the central nervous system within one year of treatment," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "Today’s positive CHMP opinion is great news for people living with ALK-positive NSCLC and brings us one step closer to providing a much needed new treatment option for people and physicians in Europe."

The EMA’s recommendation is based primarily on data from the pivotal studies NP28673 and NP28761. The studies showed that Alecensa shrank tumours in people with advanced ALK-positive NSCLC whose disease had progressed following treatment with crizotinib, overall response rate; ORR: 50.8 percent, (95% CI: 41.6%, 59.9%) and 52.2 percent (95% CI 39.7%, 64.6%) in NP28673 and NP28761, respectively. Alecensa extended the time that people lived without their disease worsening or death (progression-free survival, PFS) by 8.9 months, [5.6, 12.8] in the NP28673 study and 8.2 months, [6.3, 12.6] in the NP28761 study. In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa shrank CNS tumours that were measurable in 64.0 percent of people [95% CI: 49.2%, 77.1%]. In addition, the people whose CNS tumours shrank in response to Alecensa continued to respond for a median of 11.1 months, CNS duration of response (DOR) [95% CI: 7.6, NE]. Twenty two percent (n=11) of people achieved a complete response of their measurable CNS tumours.

Alecensa as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib

Alecensa is approved in the United States, Kuwait, Israel, Canada, Hong Kong and South Korea for the treatment of ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. Alecensa is also approved for use in Japan.. In addition, Alecensa is being explored as a first-line treatment option with the phase III ALEX and J-ALEX studies comparing Alecensa to crizotinib, the current standard of care. Results from the J-ALEX study were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and showed that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66 percent (hazard ratio [HR]=0.34, 99% CI: 0.17-0.70, p<0.0001)compared to crizotinib in this specific form of lung cancer.

Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases. 2-5

About the NP28673 study
NP28673 is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee (IRC) an ORR of 50.8 percent (95% CI: 41.6%, 60.0%), as measured by RECIST criteria.

An investigator assessment also showed tumours shrank in 51.4 percent of people who received Alecensa
In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 15.2 months (95% CI: 11.2, 24.9) (duration of response; DOR)

The median PFS for people who received Alecensa was 8.9 months (95% CI: 5.6, 12.8)
Alecensa demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least two percent of people) Grade 3 or higher adverse event was shortness of breath (dyspnoea; four percent).

About the NP28761 study
NP28761 is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee (IRC) an ORR of 52.2 percent (95% CI: 39.7%, 64.6%) as measured by RECIST criteria.

An investigator assessment showed tumours shrank in 52.9 percent of people who received Alecensa (95% CI: 41.9%, 63.7%)
In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 14.9 months (95% CI: 6.9, NE) (DOR)
The median PFS for people who received Alecensa was 8.2 months (95% CI: 6.3, 12.6)
Alecensa demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least two percent of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; eight percent), increased liver enzymes (alanine aminotransferase; six percent, and aspartate aminotransferase; five percent) and shortness of breath (dyspnoea; three percent), elevated levels of triglyceride (hypertriglyceridaemia), increased potassium level (hypokalaemia) and low levels of phosphate in the blood (hypophosphatemia; three percent). Partial blood thickening (thromboplastin; two percent) time prolonged.

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura
Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States, Japan, Kuwait, Israel, Hong Kong, Canada and South Korea for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III ALEX study of Alecensa includes a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

TG Therapeutics, Inc. Announces Publication of Clinical Data from the Phase 2 Trial of TG-1101 (ublituximab) in Combination with Ibrutinib in the British Journal of Haematology

On December 16, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the publication of clinical data from a Phase 2 study of TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody, in combination with ibrutinib, the oral BTK inhibitor, in patients with Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, DEC 16, 2016, View Source [SID1234517088]). The data, which was presented at the 2015 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, demonstrates the combination to be well tolerated with limited grade 3/4 adverse events observed. An 88% overall response rate (ORR) was reported at month 6 for all patients treated, with a 95% ORR observed in patients with high risk CLL (presence of a 17p or 11q deletion or a TP53 mutation). These data are described further in the manuscript titled, "Ublituximab (TG-1101), a novel, glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukemia: results of a phase 2 trial," which was published online today in the British Journal of Haematology. The online version of the article can be accessed at View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We want to thank Dr. Jeff Sharman and the team at the US Oncology Network for their work on this important Phase 2 study and congratulate them on this peer-reviewed publication. We believe the chemo-free combination of TG-1101 and ibrutinib is an effective and much needed treatment option for patients with high-risk CLL who continue to exhibit a poor prognosis, and the data in this publication underscores our belief. The results from this study support the GENUINE Phase 3 study, and given the dramatic and rapid responses seen in this Phase 2, we are confident in the success of GENUINE. We recently announced the completion of enrollment in the revised GENUINE trial and look forward to announcing top line data in the first half of 2017," stated Michael S. Weiss, the Company’s Executive Chairman and Interim Chief Executive Officer.

"While ibrutinib is effective in patients with CLL, it is not the only answer. In this study, the addition of ublituximab to ibrutinib not only produced high response rates, but also allowed patients to achieve deeper responses with complete responses and minimal residual disease (MRD) negativity seen, which is rare with ibrutinib alone. We look forward to exploring how the increased depth of response may affect the sequence of treatments given to patients," stated Dr. Jeff Sharman, Medical Director of Hematology Research for the US Oncology Network.